Project title: Center of Excellence for Cancer Research at Taipei Veterans General Hospital phase II: Integrated approach to reduce cancer incidence and mortality

Program title: Translational Research on Novel Targets and Therapy for Triple Negative Breast Cancer (TNBC).

Translational Research on novel Targets and Therapy for Triple Negative Breast Cancer (TNBC)

Ling-Ming Tseng1, Chun-Yu Liu2 , Hsin-Chen Lee4, Shih-Chieh Hung3 , Jen-Hwey Chiu1,5

曾令民 ，劉峻宇，李新城，洪士杰，邱仁輝

1Department of Surgery, 2Division of Hematology and Oncology, Department of Medicine, 3Department of Medical Research and Education, Taipei Veterans General Hospital; 4Institute of Pharmacology, 5Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

In our previous MOHW grant (103-106) we aimed to study triple-negative breast cancer (TNBC) with 4 themes: (1) Interference of mitochondrial stress signaling in TNBC progression. (2) Targeting epithelial-mesenchymal transition in early metastatic TNBC. (3) Identification of biomarkers and therapeutic targets for recurrent TNBC. (4) Development of novel phosphatase-related agents in TNBC therapy. We found cystine deprivation induces necroptosis and ferroptosis by interfering cancer mitochondria. Cancer stem cells initiate tumor and metastasis via PP2A-STAT3 mechanisms. In particular, we found characteristic molecular subtyping in Taiwanese TNBC patients differing from Western population, and molecular characteristics of recurrent TNBC, including novel pathway such as BDNF-TrkB signaling and gene expression profiling. Preclinically, we developed phosphatase-related pathways such as SHP-1/p-STAT3, PP2A/p-Akt as anti-TNBC therapy, and found some “repurposing” agents such as nintedanib, an approved anti-pulmonary fibrotic drug, that induce TNBC cell death by SHP-1/p-STAT3 pathway. In summary we have fruitful results in basic and translational research fund by the MOHW grant (103-106), and published a total of 21 SCI journal articles. A selection of some important contribution was illustrated as figure below